药学学报
藥學學報
약학학보
ACTA PHARMACEUTICA SINICA
2005年
1期
57-64
,共8页
侯振清%张镇西%徐正红%张红%仝泽峰%冷玉珊
侯振清%張鎮西%徐正紅%張紅%仝澤峰%冷玉珊
후진청%장진서%서정홍%장홍%동택봉%랭옥산
口服给药%胰岛素%聚氰基丙烯酸正丁酯%纳米粒%稳定性%降血糖作用
口服給藥%胰島素%聚氰基丙烯痠正丁酯%納米粒%穩定性%降血糖作用
구복급약%이도소%취청기병희산정정지%납미립%은정성%강혈당작용
oral administration%insulin%polybutylcyanoacrylate%nanoparticles%stability%hypoglycemic effect
目的通过对胰岛素聚氰基丙烯酸正丁酯纳米粒(IPN)在油介质(含有0.5%吐温-20和5%维生素E的豆油)中的稳定性及其口服后对链脲霉素引起的糖尿病大鼠降血糖作用的研究,希望得到一种稳定而有效的胰岛素纳米粒口服制剂.方法依据IPN中的胰岛素含量,IPN的平均粒径和粒子跨度,及其体外释药来评估其稳定性.将IPN分散在含有0.5%吐温-20,pH2.0的水溶液中作为对照.结果研究表明,不论样品是在(25±2)℃条件下避光放置1年,还是在体外与3种消化道酶37℃酶解30 min,油介质中的IPN都比水介质中IPN稳定性好.依据单剂量po给药后,在0-144h血糖降低的百分数与时间曲线上面积(AAC)可知,po IPN的油溶液(50u·kg-1)相对于sc胰岛素(2 u·kg-1)的生物利用度为22.4%,明显高于po IPN水溶液的相对生物利用度(15.5%).结论分散在油介质中的IPN具有较好的稳定性和相对较高的生物利用度,因此,含有0.5%吐温-20和5%的维生素E的豆油有望成为口服胰岛素聚氰基丙烯酸正丁酯纳米粒的有效而稳定的分散介质.
目的通過對胰島素聚氰基丙烯痠正丁酯納米粒(IPN)在油介質(含有0.5%吐溫-20和5%維生素E的豆油)中的穩定性及其口服後對鏈脲黴素引起的糖尿病大鼠降血糖作用的研究,希望得到一種穩定而有效的胰島素納米粒口服製劑.方法依據IPN中的胰島素含量,IPN的平均粒徑和粒子跨度,及其體外釋藥來評估其穩定性.將IPN分散在含有0.5%吐溫-20,pH2.0的水溶液中作為對照.結果研究錶明,不論樣品是在(25±2)℃條件下避光放置1年,還是在體外與3種消化道酶37℃酶解30 min,油介質中的IPN都比水介質中IPN穩定性好.依據單劑量po給藥後,在0-144h血糖降低的百分數與時間麯線上麵積(AAC)可知,po IPN的油溶液(50u·kg-1)相對于sc胰島素(2 u·kg-1)的生物利用度為22.4%,明顯高于po IPN水溶液的相對生物利用度(15.5%).結論分散在油介質中的IPN具有較好的穩定性和相對較高的生物利用度,因此,含有0.5%吐溫-20和5%的維生素E的豆油有望成為口服胰島素聚氰基丙烯痠正丁酯納米粒的有效而穩定的分散介質.
목적통과대이도소취청기병희산정정지납미립(IPN)재유개질(함유0.5%토온-20화5%유생소E적두유)중적은정성급기구복후대련뇨매소인기적당뇨병대서강혈당작용적연구,희망득도일충은정이유효적이도소납미립구복제제.방법의거IPN중적이도소함량,IPN적평균립경화입자과도,급기체외석약래평고기은정성.장IPN분산재함유0.5%토온-20,pH2.0적수용액중작위대조.결과연구표명,불론양품시재(25±2)℃조건하피광방치1년,환시재체외여3충소화도매37℃매해30 min,유개질중적IPN도비수개질중IPN은정성호.의거단제량po급약후,재0-144h혈당강저적백분수여시간곡선상면적(AAC)가지,po IPN적유용액(50u·kg-1)상대우sc이도소(2 u·kg-1)적생물이용도위22.4%,명현고우po IPN수용액적상대생물이용도(15.5%).결론분산재유개질중적IPN구유교호적은정성화상대교고적생물이용도,인차,함유0.5%토온-20화5%적유생소E적두유유망성위구복이도소취청기병희산정정지납미립적유효이은정적분산개질.
Aim To study the stability of insulin-loaded polybutylcyanoacrylate nanoparticles (IPN) in an oily medium ( soybean oil containing 0. 5 % (v/v) Tween-20 and 5 % (v/v) Vitamin E) along with the hypoglycemic effect following their oral administration to streptozotocin (STZ) induced diabetic rats. Methods The stability of IPN in the process was appraised by measurement of the amount of undegraded insulin associated to nanoparticles, the average size and the span of IPN, as well as the release of insulin from IPN. IPN in an aqueous medium (containing 0. 5% (v/v) Tween-20 ) at pH 2. 0 was also investigated as control. Results The study showed that IPN in the oily medium was more stable than that in the aqueous medium over one year of storage in the dark at (25 ± 2) ℃ and the in vitro stability of IPN in the oily medium against degradation by proteolytic enzymes was much better than that in the aqueous medium. The apparent bioavailability of an oral administration of IPN (50 u · kg-1 ) in the oily medium versus an (sc) injection of insulin (2 u · kg-1 ) was 22.4%, much higher than that of IPN in the aqueous medium (15.5%), based on decreased areas above curve (AAC) determination for the blood glucose depression from time zero to 144 h of a single oral administration of IPN to STZ-diabetic rats. Conclusion IPN in soybean oil containing Tween-20 (0. 5% v/v) and Vitamin E (5% v/v) could be considered as an effective and stable delivery system for oral insulin.
